Atrial proarrhythmic effect of lead as one of the PM10 metal components of air pollution. An in-silico study.

Particulate matter (PM) is considered the most severe environmental pollution problem due to its serious effects on human health associated with an increased risk of cardiovascular morbidity and mortality. In this work, a physicochemical characterization of PM10 from the city of Medellin was developed. The results evince that lead (Pb) is one of the most abundant elements since it is present in all analyzed samples. Therefore, Pb was chosen to perform an in-silico study to assess its effects on atrial arrhythmias generation. For this purpose, we developed a model representing the Pb2+ blocking effect on the L-type calcium channel. This formulation was incorporated in a human atrial cell mathematical model and in 2D and 3D models of human atria. The simulations showed a proarrhythmic effect at high Pb2+ concentrations, through shortening of action potential duration inducing the generation of reentrant activity and atrial flutter. The results contribute to the knowledge about the cardiac physiopathological processes, triggered by lead as one of the main PM10 metal components of air pollution, that yields the generation of arrhythmias.

The Effects of Fibrotic Cell Type and Its Density on Atrial Fibrillation Dynamics: An In Silico Study.

Remodeling in atrial fibrillation (AF) underlines the electrical and structural changes in the atria, where fibrosis is a hallmark of arrhythmogenic structural alterations. Fibrosis is an important feature of the AF substrate and can lead to abnormal conduction and, consequently, mechanical dysfunction. The fibrotic process comprises the presence of fibrotic cells, including fibroblasts, myofibroblasts and fibrocytes, which play an important role during fibrillatory dynamics. This work assesses the effect of the diffuse fibrosis density and the intermingled presence of the three types of fibrotic cells on the dynamics of persistent AF. For this purpose, the three fibrotic cells were electrically coupled to cardiomyocytes in a 3D realistic model of human atria. Low (6.25%) and high (25%) fibrosis densities were implemented in the left atrium according to a diffuse fibrosis representation. We analyze the action potential duration, conduction velocity and fibrillatory conduction patterns. Additionally, frequency analysis was performed in 50 virtual electrograms. The tested fibrosis configurations generated a significant conduction velocity reduction, where the larger effect was observed at high fibrosis density (up to 82% reduction in the fibrocytes configuration). Increasing the fibrosis density intensifies the vulnerability to multiple re-entries, zigzag propagation, and chaotic activity in the fibrillatory conduction. The most complex propagation patterns were observed at high fibrosis densities and the fibrocytes are the cells with the largest proarrhythmic effect. Left-to-right dominant frequency gradients can be observed for all fibrosis configurations, where the fibrocytes configuration at high density generates the most significant gradients (up to 4.5 Hz). These results suggest the important role of different fibrotic cell types and their density in diffuse fibrosis on the chaotic propagation patterns during persistent AF.

Electroanatomical mapping based on discrimination of electrograms clusters for localization of critical sites in atrial fibrillation.

Locating critical sites on the atrial surface during AF to guide the ablation procedures is an open problem. Electrogram-guided approaches have been proposed. However, electrograms (EGM) are complex and not well-described type of signals and anatomically-based pulmonary vein isolation remains been recommended as the cornerstone procedure. We introduce a method that builds an electroanatomical map to visualize the distribution of different morphological patterns of the EGM signals over the atrial surface. The proposed scheme uses EGM signals recorded with a commercial cardiac mapping. Likewise, two morphological and two non-linear features are computed from each single EGM. Patterns are discriminated using a semi-supervised clustering approach that does not need a priory definition of EGM morphologies or classes. The method was tested under two scenarios: a set of EGM signals recorded in AF patients and a set of signals obtained from 2D simulations of atrial conduction sustained by rotors. Our method was able to locate the clusters in a map of the atrial surface of each patient. These locations allow the specialist to study the distribution of critical AF sites. The method was able to locate the pivot point of the rotors in the 2D models. Our results suggest that the proposed method is a potential assisting tool for guided ablation procedures. Further clinical studies are needed to establish the relationship between clusters and arrhythmogenic substrates in AF, and to validate the usefulness of the method to locate critical conduction sites in patients.

Entropy Mapping Approach for Functional Reentry Detection in Atrial Fibrillation: An In-Silico Study.

Catheter ablation of critical electrical propagation sites is a promising tool for reducing the recurrence of atrial fibrillation (AF). The spatial identification of the arrhythmogenic mechanisms sustaining AF requires the evaluation of electrograms (EGMs) recorded over the atrial surface. This work aims to characterize functional reentries using measures of entropy to track and detect a reentry core. To this end, different AF episodes are simulated using a 2D model of atrial tissue. Modified Courtemanche human action potential and Fenton-Karma models are implemented. Action potential propagation is modeled by a fractional diffusion equation, and virtual unipolar EGM are calculated. Episodes with stable and meandering rotors, figure-of-eight reentry, and disorganized propagation with multiple reentries are generated. Shannon entropy ( S h E n ), approximate entropy ( A p E n ), and sample entropy ( S a m p E n ) are computed from the virtual EGM, and entropy maps are built. Phase singularity maps are implemented as references. The results show that A p E n and S a m p E n maps are able to detect and track the reentry core of rotors and figure-of-eight reentry, while the S h E n results are not satisfactory. Moreover, A p E n and S a m p E n consistently highlight a reentry core by high entropy values for all of the studied cases, while the ability of S h E n to characterize the reentry core depends on the propagation dynamics. Such features make the A p E n and S a m p E n maps attractive tools for the study of AF reentries that persist for a period of time that is similar to the length of the observation window, and reentries could be interpreted as AF-sustaining mechanisms. Further research is needed to determine and fully understand the relation of these entropy measures with fibrillation mechanisms other than reentries.

Atrial Rotor Dynamics Under Complex Fractional Order Diffusion.

The mechanisms of atrial fibrillation (AF) are a challenging research topic. The rotor hypothesis states that the AF is sustained by a reentrant wave that propagates around an unexcited core. Cardiac tissue heterogeneities, both structural and cellular, play an important role during fibrillatory dynamics, so that the ionic characteristics of the currents, their spatial distribution and their structural heterogeneity determine the meandering of the rotor. Several studies about rotor dynamics implement the standard diffusion equation. However, this mathematical scheme carries some limitations. It assumes the myocardium as a continuous medium, ignoring, therefore, its discrete and heterogeneous aspects. A computational model integrating both, electrical and structural properties could complement experimental and clinical results. A new mathematical model of the action potential propagation, based on complex fractional order derivatives is presented. The complex derivative order appears of considering the myocardium as discrete-scale invariant fractal. The main aim is to study the role of a myocardial, with fractal characteristics, on atrial fibrillatory dynamics. For this purpose, the degree of structural heterogeneity is described through derivatives of complex order γ = α + jß. A set of variations for γ is tested. The real part α takes values ranging from 1.1 to 2 and the imaginary part ß from 0 to 0.28. Under this scheme, the standard diffusion is recovered when α = 2 and ß = 0. The effect of γ on the action potential propagation over an atrial strand is investigated. Rotors are generated in a 2D model of atrial tissue under electrical remodeling due to chronic AF. The results show that the degree of structural heterogeneity, given by γ, modulates the electrophysiological properties and the dynamics of rotor-type reentrant mechanisms. The spatial stability of the rotor and the area of its unexcited core are modulated. As the real part decreases and the imaginary part increases, simulating a higher structural heterogeneity, the vulnerable window to reentrant is increased, as the total meandering of the rotor tip. This in silico study suggests that structural heterogeneity, described by means of complex order derivatives, modulates the stability of rotors and that a wide range of rotor dynamics can be generated.

Effect of the electrograms density in detecting and ablating the tip of the rotor during chronic atrial fibrillation: an in silico study.

AIMS: Identification in situ of arrhythmogenic mechanisms could improve the rate of ablation success in atrial fibrillation (AF). Our research group reported that rotors could be located through dynamic approximate entropy (DApEn) maps. However, it is unknown how much the spatial resolution of catheter electrodes could affect substrates localization. The present work looked for assessing the electrograms (EGMs) spatial resolution needed to locate the rotor tip using DApEn maps. METHODS AND RESULTS: A stable rotor in a two-dimensional computational model of human atrial tissue was simulated using the Courtemanche electrophysiological model and implementing chronic AF features. The spatial resolution is 0.4 mm (150 × 150 EGM). Six different lower resolution arrays were obtained from the initial mesh. For each array, DApEn maps were constructed using the inverse distance weighting (IDW) algorithm. Three simple ablation patterns were applied. The full DApEn map detected the rotor tip and was able to follow the small meander of the tip through the shape of the area containing the tip. Inverse distance weighting was able to reconstruct DApEn maps after applying different spatial resolutions. These results show that spatial resolutions from 0.4 to 4 mm accurately detect the rotor tip position. An ablation line terminates the rotor only if it crosses the tip and ends at a tissue boundary. CONCLUSION: A previous work has shown that DApEn maps successfully detected simulated rotor tips using a high spatial resolution. In this work, it was evinced that DApEn maps could be applied using a spatial resolution similar to that available in commercial catheters, by adding an interpolation stage. This is the first step to translate this tool into medical practice with a view to the detection of ablation targets.

Dynamic approximate entropy electroanatomic maps detect rotors in a simulated atrial fibrillation model.

There is evidence that rotors could be drivers that maintain atrial fibrillation. Complex fractionated atrial electrograms have been located in rotor tip areas. However, the concept of electrogram fractionation, defined using time intervals, is still controversial as a tool for locating target sites for ablation. We hypothesize that the fractionation phenomenon is better described using non-linear dynamic measures, such as approximate entropy, and that this tool could be used for locating the rotor tip. The aim of this work has been to determine the relationship between approximate entropy and fractionated electrograms, and to develop a new tool for rotor mapping based on fractionation levels. Two episodes of chronic atrial fibrillation were simulated in a 3D human atrial model, in which rotors were observed. Dynamic approximate entropy maps were calculated using unipolar electrogram signals generated over the whole surface of the 3D atrial model. In addition, we optimized the approximate entropy calculation using two real multi-center databases of fractionated electrogram signals, labeled in 4 levels of fractionation. We found that the values of approximate entropy and the levels of fractionation are positively correlated. This allows the dynamic approximate entropy maps to localize the tips from stable and meandering rotors. Furthermore, we assessed the optimized approximate entropy using bipolar electrograms generated over a vicinity enclosing a rotor, achieving rotor detection. Our results suggest that high approximate entropy values are able to detect a high level of fractionation and to locate rotor tips in simulated atrial fibrillation episodes. We suggest that dynamic approximate entropy maps could become a tool for atrial fibrillation rotor mapping.

IDENTIFICACIÓN DE ZONAS SUSCEPTIBLES DE ABLACIÓN EN FIBRILACIÓN AURICULAR PERMANENTE IMPLEMENTANDO ENTROPÍA APROXIMADA EN UN MODELO 2D / IDENTIFICATION OF TARGET SITES FOR ABLATION DURING PERMANENT ATRIAL FIBRILLATION IMPLEMENTING APPROXIMATE ENTROPY IN A 2D MODEL / IDENTIFICAÇÃO DE ÁREAS SUSCETÍVEIS DE ABLAÇÃO PERMANENTE DE FIBRILAÇÃO ATRIAL NA IMPLEMENTAÇÃO ENTROPY APROXIMADO UM MODELO 2D

La fibrilación auricular (FA) es la arritmia cardiaca más común. La ablación con catéter se ha convertido en la principal estrategia terapéutica para el tratamiento de la FA paroxística, sin embargo, los resultados en FA permanente no son completamente satisfactorios. Se propone la ablación de los electrogramas auriculares complejos fragmentados (CFAE) para la terminación de un rotor como mecanismo de mantenimiento de FA permanente. El objetivo de este trabajo es caracterizar los CFAE mediante la implementación de entropía aproximada (ApEn) y correlacionarlos con el tip de un rotor simulado. Para esto, se desarrolló un modelo 2D de tejido de aurícula humana bajo condiciones de FA permanente; se registraron electrogramas unipolares durante la actividad del rotor y se desarrolló un algoritmo para la medida de ApEn. La ApEn permitió localizar los CFAE con una alta precisión y relacionarlos con el tip del rotor. Por lo que este índice podría ser muy eficaz en la identificación de zonas susceptibles de ablación.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Catheter ablation has become the main therapeutic strategy for the treatment of paroxysmal AF, however, results in permanent AF are not completely satisfactory. Ablation of complex fractionated atrial electrograms (CFAE) is proposed for the termination of a rotor as mechanism of permanent AF maintenance. The aim of this work is to characterize the CFAE by implementing approximate entropy (ApEn) and to correlate with the tip of a simulated rotor. For this, a 2D model of human atrial tissue under permanent FA conditions was developed. Unipolar electrograms were recorded during the rotor activity and an algorithm to measure ApEn was developed. The ApEn allowed locate the CFAE with high precision and relate them to the tip of the rotor. So this index could be very effective in identifying target sites for ablation.

A fibrilação atrial (FA) é a arritmia cardíaca mais comum. A ablação por cateter tornou-se a principal estratégia terapêutica para o tratamento da fibrilação atrial paroxística, no entanto, resulta em FA permanente não são completamente satisfatórios. Ablação de fones de ouvido eletrocardiogramas complexos fragmentada (CFAE) para a conclusão de um rotor como um mecanismo de manutenção da FA permanente, é proposto. O objetivo deste trabalho é caracterizar o CFAE através da implementação de entropia aproximada (ApEn) e correlacioná-los com a ponta de um rotor simulado. Para isso, um modelo em 2D do tecido atrial humano sob condições de FA permanente desenvolvido; unipolares electrogramas foram registados durante a actividade do rotor e um algoritmo para medir ApEn desenvolvido. O ApEn permitido CFAE localizar com precisão elevada e relacioná-los com a ponta do rotor. Portanto, esta taxa pode ser muito eficaz na identificação de áreas suscetíveis a ablação.